Modifiable Risk Factors for Hepatocellular Carcinoma in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-Analysis.

Background and Aims: The increasing incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to a gradual increase in MASLD-related hepatocellular carcinomas (HCC). In this context, we aimed to investigate the association between modifiable factors and the risk of incident HCC in patients with MASLD.
Methods: Two authors independently searched electronic databases (PubMed, Embase, and the Cochrane Library) from their inception to April 1, 2023. Observational studies reporting an association between modifiable risk factors and MASLD-related HCC were eligible for inclusion. The effect size on the study outcomes was calculated using a random-effects model and was presented as a risk ratio with 95% confidence interval.
Results: A total of 31 studies covering 1.02 million individuals were included. Regarding lifestyle factors, smoking and alcohol consumption were associated with 30% (1.30 [1.08-1.57]) and 140% (2.41 [1.03-5.65]) risk increase of MASLD-related HCC. Regarding metabolic risk factors, patients with MASLD who were overweight or obese (1.31 [1.13-1.52]), had diabetes (2.08 [1.71-2.53]) and hypertension (1.42 [1.12-1.80]) had a higher risk of developing HCC, while dyslipidemia was negatively associated with MASLD-HCC (0.78 [0.65-0.93]). The use of metformin, statin, and aspirin was associated with 18% (0.82 [0.68-0.98]), 55% (0.45 [0.36-0.56]), and 36% (0.64 [0.44-0.92]) risk reduction in incident HCC, respectively.
Conclusions: This comprehensive systematic review and meta-analysis showed statistically significant increases in the risk of incident HCC inpatients with MASLD due to smoking, alcohol use, obesity, diabetes, and hypertension, whereas metformin, statin, and aspirin therapy might modify disease progression.
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